2005 Fiscal Year Final Research Report Summary
The basic research and clinical trial of therapeutic angiogenesis using bone marrow implantation with EPO
| Project/Area Number |
16590665
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Niigata University |
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Principal Investigator |
KATO Kiminori Niigata University, Medical and Dental Hospital, Assistant, 医歯学総合病院, 助手 (00303165)
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| Co-Investigator(Kenkyū-buntansha) |
HANAWA Haruo Niigata University, Institute of Medicine and Dentistry, Lecturer, 医歯学系, 講師 (40282983)
KODAMA Makoto Niigata University, Institute of Medicine and Dentistry, Associate Professor, 医歯学系, 助教授 (10242447)
NAKAZAWA Mikio Niigata University, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (80143759)
TOBA Ken Niigata University, Medical and Dental Hospital, Lecturer, 医歯学総合病院, 講師 (60313540)
AIZAWA Yoshifusa Niigata University, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (50143780)
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| Project Period (FY) |
2004 – 2005
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| Keywords | angiogenesis / erythropoietin / erythroblast / CD14 positive cell / CD34 positive cell / VEGF / PLGF |
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| Research Abstract |
A. Clinical trial of bone marrow implantation (BMI) accompanied with erythropoietin (EPO) injection
(1) The results of monotherapy of BMI and combination therapy of BMI and EPO 6,000 IU : EPO injection did not cause major side effects, and no additional effects were observed in the combination therapy compared with the monotherapy. We reported that the number of implanted CD34-positive cells was one of the primary factors that influenced the clinical efficacy of BMI. (Circ J 2004;68:1189-93)
(2) The results of combination therapy of BMI and high dose EPO 24,000IU : Four patients participated. A patient who had been previously treated with the monotherapy one year ago was treated again with the high dose combination therapy. The change of ankle-brachial pressure index revealed the superiority of the high dose combination : monotherapy, 0→0, and the high dose combination, 0→0.67. However, the other 3 patients showed any additional effect of the high dose EPO. Then we tried a combination th
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erapy of BMI and a sequential administration of EPO to obtain prolonged effects of EPO in the ischemic organs.
(3) The results of the combination therapy of BMI and EPO 6,000 IU x 5-days : Four patients participated. One of them showed the improvement of rest pain, but the others did not, and suffered from leg amputation, later. Further device of combination therapy is necessary for such serious patients.
B. Basic research of the mechanism of angiogenesis by erythroblasts and EPO
(1) The additional effect of EPO to BMI (in vivo) : A murine model of limb ischemia was studied. Simultaneous administration of EPO with BMI enhanced angiogenesis by the implanted erythroblasts through further secretion of angiogenic factors by the cells (JMCC 2006:40:629-38).
(2) The facts as stated above (in vitro) : In vitro angiogenesis was performed. Erythroblastic colonies made beforehand from human hematopoietic stem cells produced capillary-like networks around them. The addition of EPO further enhanced the angiogenesis presumably through surviving effects on erythroblasts (JMCC 2006:40:629-38).
(3) The essential role of erythroblast in angiogenesis : Ischemic limbs did not survive in mice transplanted with erythroid-depleted bone marrow cells, hence erythroblasts were essential for the effect in vivo. Limbs did not survive unexpectedly in mice transplanted with purified erythroid cells, and the effects recovered by the simultaneous implantation of CD14-positive bone marrow cells. Therefore the angiogenic effects of BMI arose from the implanted erythroid cells in the presence of the assistance of macrophages (JMCC 2006:40:629-38). Less
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Research Products
(13 results)
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[Journal Article] Erythroid cells play essential roles in angiogenesis by bone marrow cell implantation.2006
Author(s)
Ozawa T, Toba K, Kato K, Minagawa S, Saigawa T, Hanawa H, Makiyama Y, Moriyama M, Honma K, Isoda M, Hasegawa G, Naito M, Takahashi M, Aizawa Y.
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Journal Title
J Mol Cell Cardiol 40
Pages: 629-638
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Marked decrease of plasma VEGF after implantation of autologous bone marrow mononuclear cells in a patient with critical limb ischemia-a case report.2006
Author(s)
Ozawa T, Kato K, Sanada H, Makiyama Y, Saigawa T, Souda S, Hashimoto S, Furukawa T, Toba K, Kodama M, Fujiwara H, Namura O, Hayashi J, Yoshimura N, Aizawa Y.
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Journal Title
Angiology 57
Pages: 235-239
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Amiodarone improves cardiac sympathetic nerve function to hold norepinephrine in the heart, prevents left ventricular remodeling, and improves cardiac function in rat dilated cardiomyopathy.2005
Author(s)
Tachikawa H, Kodama M, Watanabe K, Takahashi T, Ma M, Kashimura T, Ito M, Hirono S, Okura Y, Kato K, Hanawa H, Aizawa Y.
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Journal Title
Circulation 111
Pages: 894-899
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Effect of hydrodynamics-based gene delivery of plasmid DNA encoding interleukin-1 receptor antagonist-Ig for treatment of rat autoimmune myocarditis : possible mechanism for lymphocytes and noncardiac cells.2005
Author(s)
Liu H, Hanawa H, Yoshida T, Elnaggar R, Hayashi M, Watanabe R, Toba K, Yoshida K, Chang H, Okura Y, Kato K, Kodama M, Maruyama H, Miyazaki J, Nakazawa M, Aizawa Y.
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Journal Title
Circulation 111
Pages: 1593-1600
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Sensitive measurement of fragmented red cell population using flow cytometry, and its application for estimating thrombotic microangiopathy after stem cell transplantation.2004
Author(s)
Toba K, Tsuchiyama J, Hashimoto S, Ichida T, Kato K, Watanabe K, Furukawa T, Narita M, Takahashi M, Aizawa Y.
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Journal Title
Cytometry 58B
Pages: 39-46
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Clinical application of bone marrow implantation in patients with arteriosclerosis obliterans, and the association between efficacy and the number of implanted bone marrow cells.2004
Author(s)
Saigawa T, Kato K, Ozawa T, Toba K, Makiyama Y, Minagawa S, Hashimoto S, Furukawa T, Nakamura Y, Hanawa H, Kodama M, Yoshimura N, Fujiwara H, Namura O, Sogawa M, Hayashi J, Aizawa Y.
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Journal Title
Circ J. 68
Pages: 1189-1193
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of coxsackievirus and adenovirus receptor in neointima of the rat carotid artery.2004
Author(s)
Nasuno A, Toba K, Ozawa T, Hanawa H, Osman Y, Hotta Y, Yoshida K, Saigawa T, Kato K, Kuwano R, Watanabe K, Aizawa Y.
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Journal Title
Cardiovasc Pathol. 13
Pages: 79-84
Description
「研究成果報告書概要(欧文)」より
